The excessive production of peroxynitrite (ONOO- ) anion is well-known to play a significant role in numerous diseases including chronic inflammation, Type II Diabetes Mellitus (T2DM), Alzheimer's, and Parkinson's. The highly reactive peroxynitrite (PN) is known to nitrate and oxidize proteins, lipids, and nucleotides thus generating toxicity. Thus, our objective was to design and synthesize complexes that can attenuate the toxic effects of PN in vivo in vivo for pharmacological studies and potential therapeutic strategies. Redox-active Manganese(III) complexes of bis(hydroxyphenyl) dipyrromethenes (Mn(III)–DPMs) are able to catalytically destroy PN by converting PN to nitrite ion through a two electron mechanism. Herein, synthetic methods for preparing functionalized Mn(III)–DPMs with enhanced solubility and a conjugation site for the attachment of biomolecules were studied. Since both Mn(III)–DPMs and peroxisome proliferation-activated receptor γ (PPARγ) agonist have been shown to be active and effective in treating type II diabetes mellitus, we hypothesized that the conjugate of our Mn(III)–DPM and a functional PPARγ agonist of the PPAR receptor may have a synergistic effect in this condition. In addition, if synergistic action is observed it may be possible to reduce to dose of PPARγ agonist. Structure–activity studies using boronate oxidation and the prevention-of-nitration assays were used to determine catalytic activity and the characteristics of these assays were examined and improved. In addition, the development oxidant-triggered aza-bis(hydroxylphenyl)dipyrromethene (aza–DPM) pro-catalyst systems was also explored.
|Advisor:||Neumann, William L.|
|Commitee:||Kwon, Gium, Lu, Yun, Nieto, Marcelo|
|School:||Southern Illinois University at Edwardsville|
|School Location:||United States -- Illinois|
|Source:||MAI 54/03M(E), Masters Abstracts International|
|Subjects:||Organic chemistry, Pharmacy sciences|
|Keywords:||Alzheimer’s disease, Chronic inflammation, Parkinson’s disease|
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